Spray freeze drying (SFD) was evaluated as bulk production process in the development of orodispersible probiotic tablets. The technology encompasses spray freezing into cold vapour followed by rotational bulk freeze drying. Three nozzle diameters, i.e. 220 µm, 300 µm and 400 µm, were used to produce fresh probiotic bulk powder, yielding microspherical particles with respective diameters of 385 µm, 556 µm and 654 µm. The SFD formulation constisted out of trehalose, PBS and probiotic cells. Subsequently, these powders were used in a compaction simulator to investigate their compressability and tabletting behaviour. Round flat-faced tablets were manufactured using a die with a diameter of 10 mm, and the fill volume was set to obtain a tablet mass of about 275 mg. The uniaxial compaction force was varied from 1.0 kN up to 10.0 kN in incremental steps of 1.0 kN, corresponding to compaction pressures ranging from 12.7 to 127.3 MPa. Heckel analysis revealed a yield pressure of 98 MPa when compacting the SFD powders. Moreover, low compaction force of only 28.2 MPa should be applied to obtain tablets of acceptable tablet tensile strength of 1.7MPa, suited for further processing according to industrial standards. The low compaction pressure contributed to the stability of the bacterial cells during storage, with a final bacterial concentration in the tablets of 7.8 log CFU/g after 6 months of storage at 4°C and ambient relative humidity. Even a slight compaction force of 1 kN appeared to benefit the stability compared to the loose powder state. Furthermore, the compacts’ disintegration time at the recommended TTS of 1.7MPa appeared to be below 60 seconds, meeting Ph. Eur. requirements regarding orodispersible tablet disintegration time. In conclusion, these findings validate the novel application of SFD bulk powders in tabletting processes, proving SFD to be a highly viable and robust formulation strategy for probiotic tablets.